Abstract

Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

Highlights

  • Continuous renal replacement therapy (CRRT) is commonly used in critically ill patients with acute kidney injury (AKI) due to life-threatening fluid overload and/or electrolyte abnormalities.Mortality rate from septic shock is still high (60%), despite the advancement in medicine [1]

  • Many drugs used in critically ill patients with AKI can be titrated to effect

  • This paper will focus on antibiotic agents and how to optimize antibiotic dosing strategies depending on their pharmacodynamics (PD) targets

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Summary

Introduction

Continuous renal replacement therapy (CRRT) is commonly used in critically ill patients with acute kidney injury (AKI) due to life-threatening fluid overload and/or electrolyte abnormalities. Mortality rate from septic shock is still high (60%), despite the advancement in medicine [1]. Sepsis Surviving Guideline suggests clinicians to administer the appropriate dose of antibiotic as soon as the septic shock is recognized [2]. Many drugs used in critically ill patients with AKI can be titrated to effect (pain medications, sedatives, and vasopressors). The serum concentrations of most antibiotics cannot be measured or titrated in the clinical setting. The empiric dosing regimen must be correct with the first dose. This paper will focus on antibiotic agents and how to optimize antibiotic dosing strategies (time- vs concentration-dependent) depending on their pharmacodynamics (PD) targets

Drug Dosing Challenges for Clinicians
Pharmacokinetic Changes in Critically Ill Patients with Sepsis
Types of Renal Replacement Therapy
Drug Specific Considerations
Drug Administration Strategies
Findings
Conclusions

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